Progestin treatment in the dog II. Effects on the hypothalamic–pituitary–adrenocortical axis

Selman PJ, Mol JA, Rutteman GR, Rijnberk A. Progestin treatment in the dog. II. Effects on the hypothalamic–pituitary–adrenocortical axis. Eur J Endocrinol 1994;131:422–30. ISSN 0804–4643 The effects of two synthetic progestins, medroxyprogesterone acetate (MPA) and proligestone (PROL), on the hypothalamic–pituitary–adrenocortical (HPA) axis were studied in two groups of eight ovariohysterectomized dogs each. Eight injections of long-acting progestins were administered at 3-week intervals. Recovery of the HPA axis was studied in four dogs of each group in the following 6 months. Basal levels of adrenocorticotrophin (ACTH) and cortisol in plasma and the urinary corticoid/creatinine ratio were measured. The responsiveness of the HPA axis was investigated by stimulation with ovine corticotrophin-releasing hormone. Both MPA and PROL caused sawtooth patterns of supression of basal ACTH and cortisol levels in plasma, synchronous with the time of administration. The suppression of the adrenocortical component of the HPA axis was most pronounced. Adrenocorticotrophin production also was affected but to a lesser extent and occurred especially in PROL-treated dogs. Soon after the cessation of progestin administration ACTH levels increased, sometimes with a rebound. In both groups basal cortisol levels and urinary corticoid/creatinine ratios did not return to pretreatment levels until 6 months after the last progestin injection. It is concluded that MPA and PROL act as glucocorticoid agonists and suppress the HPA axis. The suppression at the adrenocortical level may last for 6 months. JA Mol, Department of Clinical Sciences of Companion Animals, Utrecht University, PO Box 80.154, 3508 TD Utrecht, The Netherlands

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Hypothalamic-pituitary-adrenal axis function in patients with bipolar disorder

The British Journal of Psychiatry ◽

10.1192/bjp.184.6.496 ◽

2004 ◽

Vol 184 (6) ◽

pp. 496-502 ◽

Cited By ~ 227

Author(s):

Stuart Watson ◽

Peter Gallagher ◽

James C. Ritchie ◽

I. Nicol Ferrier ◽

Allan H. Young

Keyword(s):

Bipolar Disorder ◽

Hpa Axis ◽

Cortisol Response ◽

Hypothalamic Pituitary Adrenal ◽

The Core ◽

Basal Cortisol ◽

Suppression Test ◽

Cortisol Levels ◽

Dexamethasone Suppression ◽

Pituitary Adrenal Axis

BackgroundHypothalamic-pituitary-adrenal (HPA) axis function, as variously measured by the responses to the combined dexamethasone/ corticotrophin-releasing hormone (dex/ CRH) test, the dexamethasone suppression test (DST) and basal cortisol levels, has been reported to be abnormal in bipolar disorder.AimsTo test the hypothesis that HPA axis dysfunction persists in patients in remission from bipolar disorder.MethodSalivary cortisol levels and the plasma cortisol response to the DST and dex/CRH test were examined in 53 patients with bipolar disorder, 27 of whom fulfilled stringent criteria for remission, and in 28 healthy controls. Serum dexamethasone levels were measured.ResultsPatients with bipolar disorder demonstrated an enhanced cortisol response to the dex/CRH test compared with controls (P=0.001). This response did not differ significantly between remitted and non-remitted patients. These findings were present after the potentially confounding effects of dexamethasone levels were accounted for.ConclusionsThe dex/CRH test is abnormal in both remitted and non-remitted patients with bipolar disorder. Thismeasure of HP Aaxis dysfunction is a potential trait marker in bipolar disorder and thus possibly indicative of the core pathophysiological process in this illness.

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Common variants of the mineralocorticoid and glucocorticoid receptor genes may contribute to pregnancy-related anxiety: a pilot study

Open Medicine ◽

10.2478/s11536-012-0101-1 ◽

2013 ◽

Vol 8 (1) ◽

pp. 117-124 ◽

Cited By ~ 1

Author(s):

Natalia Chistiakova ◽

Elena Sergienko ◽

Kirill Savost’ianov

Keyword(s):

Hpa Axis ◽

Maternal Stress ◽

Biological Effects ◽

Normal Pregnancy ◽

Common Variants ◽

Basal Cortisol ◽

Increased Risk ◽

Elisa Technique ◽

Polymorphic Variants ◽

Cortisol Levels

AbstractThe hypothalamic-pituitary-adrenal (HPA) axis overactivity is thought to contribute to increased vulnerability to maternal stress. We hypothesize that functionally relevant polymorphic variants of the glucocorticoid (NR3C1) and mineralocorticoid (NR3C2) receptor genes mediating biological effects of cortisol, a major stress hormone, could also modulate the capacity to cope with pregnancy-related anxiety. Genomic DNA from the blood of 42 women with pregnancy-related anxiety and 42 age-matched women with normal pregnancy (5–6th months of gestation) were genotyped for markers rs6195 and rs10482605 of NR3C1 and two NR3C2 polymorphisms (rs5522 and rs2070951) using a Taqman allele discrimination assay. Serum total cortisol was measured using an ELISA technique. The allele Ser363 of rs6195 (the N363S polymorphism of NR3C1) was found to be associated with a higher risk of maternal stress (odds ratio (OR)=5.27; P=0.001). For NR3C2, the allele Val180 of rs5522 (I180V) also showed association with increased risk of neonatal stress (OR=1.97; P=0.038). Both predisposing gene variants were also associated with significantly elevated levels of cortisol in normally pregnant women and females with pregnancy-related anxiety. Our results suggest that pregnancy-related anxiety can be modulated by variants of NR3C1 and NR3C2 associated with increased basal cortisol levels. Thus, our findings provide evidence in support of the suggestion that elevated cortisol levels and HPA axis hyperactivity are implicated in pregnancy-related anxiety.

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Early deprivation and home basal cortisol levels: A study of internationally adopted children

Development and Psychopathology ◽

10.1017/s0954579408000230 ◽

2008 ◽

Vol 20 (2) ◽

pp. 473-491 ◽

Cited By ~ 77

Author(s):

Darlene A. Kertes ◽

Megan R. Gunnar ◽

Nicole J. Madsen ◽

Jeffrey D. Long

Keyword(s):

Hpa Axis ◽

World Health ◽

Growth Delay ◽

Adopted Children ◽

Early Deprivation ◽

Latent Factor ◽

Basal Cortisol ◽

Internationally Adopted Children ◽

Cortisol Levels ◽

Internationally Adopted

AbstractAnimal studies reveal that early deprivation impairs regulation of the hypothalamic–pituitary–adrenocortical (HPA) axis, potentially increasing vulnerability to stressors throughout life. To examine early deprivation effects on basal HPA axis activity in humans, basal cortisol levels were examined in 164 internationally adopted children who had experienced varying degrees of preadoption deprivation. Duration of institutional care, age at adoption, and parent ratings of preadoption neglect indexed a latent factor ofDeprived Care.Adoption measures of height and weight standardized to World Health Organisation norms indexed a latent factor ofGrowth Delaythat was viewed as another reflection of deprivation. Cortisol samples were collected 3.3–11.6 years postadoption (Md= 7.3 years) at home on 3 days approximately 30 min after wakeup and before bedtime. Both early a.m. levels and the decrease in cortisol across the day were examined. A structural equation model revealed that preadoption Deprived Care predicted Growth Delay at adoption and Growth Delay predicted higher morning cortisol levels and a larger diurnal cortisol decrease.

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244 DEVELOPMENT OF SUPEROVULATORY STRATEGIES IN ALPACAS

Reproduction Fertility and Development ◽

10.1071/rdv19n1ab244 ◽

2007 ◽

Vol 19 (1) ◽

pp. 238

Author(s):

G. Gamarra ◽

A. Gallegos ◽

M. Asparrin ◽

H. W. Vivanco-Mackie

Keyword(s):

The Netherlands ◽

Medroxyprogesterone Acetate ◽

Ovarian Stimulation ◽

Animal Health ◽

Follicular Development ◽

Ovarian Response ◽

Randomized Design ◽

Progestin Treatment ◽

Group 2 ◽

Sigma Chemical

The objective of the present study was to determine the ovarian response of alpacas to different treatments for follicular development and superovulation. Twenty-nine mature, lactating alpacas, between 31 and 56 days postpartum, managed in the Peruvian highlands (altitude = 4100 m) were randomly distributed into 4 experimental groups. Groups 1 (n = 7) and 3 (n = 8) received a homemade intravaginal sponge containing 60 mg of medroxyprogesterone acetate (MAP; Sigma Chemical Co., St Louis, MO, USA) plus 2 mL of PGF2α (IM; Illiren�; Intervet International, Boxmeer, The Netherlands) on Day 0. Groups 2 (n = 7) and 4 (n = 7) received 2 mL of PGF2α (IM) on Day 0, but did not receive a MAP sponge. All groups received 6 injections (IM) of FSH (Folltropin V�; Bioniche Animal Health, Beltsville, Ontario, Canada) in decreasing dosages of 50, 50, 30, 30, 20, and 20 mg, respectively, every 12 h (at 0700 and 1900 h each day), plus 300 IU of eCG (IM; Folligon�; Intervet International) at the time of the last FSH treatment, with the aim of increasing LH levels. The FSH treatments started on Days 7, 5, 9, and 7 (from Day 0) in groups 1–4, respectively. MAP sponges were removed at the time of the last FSH treatment in groups 1 and 3. All alpacas were naturally mated twice at 12 and 24 h after the last FSH treatment. Alpacas in groups 1 and 2 received 3000 IU of hCG (IM; Corulon�; Intervet International) and alpacas of groups 3 and 4 received 2.5 mL of GnRH (IM; Conceptal�; Intervet International) immediately after the first mating. Seven days after the first mating, ovaries of all alpacas were examined by transvaginal ultrasonography. Ovarian response was estimated by determining the number of CL present on each ovary. The numbers of follicles that were at least 8 mm in diameter were also counted. Data were analyzed as a complete randomized design with 4 treatments. The average number of CL per alpaca was 1.3, 1.00, 1.00, and 0.9 for groups 1 to 4, respectively (P > 0.05). The average number of follicles that were at least 8 mm in diameter per alpaca was 9.4, 20.4, 0.9, and 3.9 for groups 1 to 4, respectively (P ≤ 0.05) with females in group 2 showing the highest response. We conclude that progestin treatment did not affect ovulatory response of lactating alpacas to exogenous gonadotropins. An effective ovarian stimulation strategy for achieving superovulation in alpacas remains to be developed.

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To Nap or Not to Nap

Biological Research For Nursing ◽

10.1177/1099800411420861 ◽

2011 ◽

Vol 15 (2) ◽

pp. 185-190 ◽

Cited By ~ 17

Author(s):

Diana Lynn Woods ◽

Haesook Kim ◽

Maria Yefimova

Keyword(s):

Hpa Axis ◽

Diurnal Rhythm ◽

Longitudinal Design ◽

Close Association ◽

Nursing Home Residents ◽

Behavioral Symptoms ◽

Basal Cortisol ◽

Significant Difference ◽

Cortisol Levels ◽

Wake State

Background: Alterations in the sleep–wake cycle, including daytime napping, are consistently reported in persons with dementia (PWD). A dysregulation in the hypothalamic–pituitary–adrenal (HPA) axis, indexed by elevated evening cortisol, may offer one explanation for these alterations. Alternatively, excessive daytime sleeping may alter cortisol rhythm and increase intraindividual variability, potentially contributing to increased environmental reactivity and behavioral symptoms. The purpose of this substudy ( N = 12) was to examine the association between daytime napping and basal cortisol diurnal rhythm in nursing home residents with dementia. Method: In this within-individual longitudinal design, saliva samples were obtained daily for 5 consecutive days upon waking and 30–45 min, 6 hr, and 12 hr after waking to obtain a cortisol diurnal rhythm. Behavior and sleep–wake state (nap/no nap) were observed and recorded every 20 min for 12 hr per day for 5 days. Results: Participants were categorized as high nappers (HNs) or low nappers (LNs). There was a significant difference in evening cortisol levels ( t = −2.38, p = .032) and continence ( t = 3.37, p = .007) between groups, with HNs exhibiting higher evening cortisol levels. There were no other significant differences in resident characteristics between the two groups. Conclusions: These data suggest a link between excessive daytime napping and elevated evening cortisol in PWD consistent with findings in children. Elevated evening cortisol is an indication of a dysregulation in the HPA axis. These preliminary data support a close association between the sleep–wake cycle and HPA-axis regulation in PWD.

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Ambient air pollutants are associated with morning serum cortisol in overweight and obese Latino youth in Los Angeles

Environmental Health ◽

10.1186/s12940-021-00713-2 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

C. M. Toledo-Corral ◽

T. L. Alderete ◽

M. M. Herting ◽

R. Habre ◽

A. K. Peterson ◽

...

Keyword(s):

Hpa Axis ◽

Air Pollutants ◽

Latino Youth ◽

Serum Cortisol ◽

Ambient Air ◽

Pubertal Status ◽

Ambient Air Pollutants ◽

Morning Cortisol ◽

Morning Serum Cortisol ◽

Cortisol Levels

Abstract Background Hypothalamic-pituitary-adrenal (HPA)-axis dysfunction has been associated with a variety of mental health and cardio-metabolic disorders. While causal models of HPA-axis dysregulation have been largely focused on either pre-existing health conditions or psychosocial stress factors, recent evidence suggests a possible role for central nervous system activation via air pollutants, such as nitrogen dioxide (NO2), ozone (O3) and particulate matter (PM). Therefore, in an observational study of Latino youth, we investigated if monthly ambient NO2, O3, and PM with aerodynamic diameter ≤ 2.5 (PM2.5) exposure were associated with morning serum cortisol levels. Methods In this cross-sectional study, morning serum cortisol level was assessed after a supervised overnight fast in 203 overweight and obese Latino children and adolescents (female/male: 88/115; mean age: 11.1 ± 1.7 years; pre-pubertal/pubertal/post-pubertal: 85/101/17; BMI z-score: 2.1 ± 0.4). Cumulative concentrations of NO2, O3 and PM2.5 were spatially interpolated at the residential addresses based on measurements from community monitors up to 12 months prior to testing. Single and multi-pollutant linear effects models were used to test the cumulative monthly lag effects of NO2, O3, and PM2.5 on morning serum cortisol levels after adjusting for age, sex, seasonality, social position, pubertal status, and body fat percent by DEXA. Results Single and multi-pollutant models showed that higher O3 exposure (derived from maximum 8-h exposure windows) in the prior 1–7 months was associated with higher serum morning cortisol (p < 0.05) and longer term PM2.5 exposure (4–10 months) was associated with lower serum morning cortisol levels (p < 0.05). Stratification by pubertal status showed associations in pre-pubertal children compared to pubertal and post-pubertal children. Single, but not multi-pollutant, models showed that higher NO2 over the 4–10 month exposure period associated with lower morning serum cortisol (p < 0.05). Conclusions Chronic ambient NO2, O3 and PM2.5 differentially associate with HPA-axis dysfunction, a mechanism that may serve as an explanatory pathway in the relationship between ambient air pollution and metabolic health of youth living in polluted urban environments. Further research that uncovers how ambient air pollutants may differentially contribute to HPA-axis dysfunction are warranted.

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Cost-effectiveness of the fixed-dose combination tiotropium/olodaterol versus tiotropium monotherapy or a fixed-dose combination of long-acting β2-agonist/inhaled corticosteroid for COPD in Finland, Sweden and the Netherlands: a model-based study

BMJ Open ◽

10.1136/bmjopen-2021-049675 ◽

2021 ◽

Vol 11 (8) ◽

pp. e049675

Author(s):

Martine Hoogendoorn ◽

Isaac Corro Ramos ◽

Stéphane Soulard ◽

Jennifer Cook ◽

Erkki Soini ◽

...

Keyword(s):

Cost Effectiveness ◽

The Netherlands ◽

Cost Effective ◽

Fixed Dose Combination ◽

Fixed Dose ◽

Inhaled Corticosteroid ◽

Dose Combination ◽

Long Acting ◽

Β2 Agonist ◽

Country Specific

ObjectivesChronic obstructive pulmonary disease (COPD) guidelines advocate treatment with combinations of long-acting bronchodilators for patients with COPD who have persistent symptoms or continue to have exacerbations while using a single bronchodilator. This study assessed the cost-utility of the fixed dose combination of the bronchodilators tiotropium and olodaterol versus two comparators, tiotropium monotherapy and long-acting β2 agonist/inhaled corticosteroid (LABA/ICS) combinations, in three European countries: Finland, Sweden and the Netherlands.MethodsA previously published COPD patient-level discrete event simulation model was updated with most recent evidence to estimate lifetime quality-adjusted life years (QALYs) and costs for COPD patients receiving either tiotropium/olodaterol, tiotropium monotherapy or LABA/ICS. Treatment efficacy covered impact on trough forced expiratory volume in 1 s (FEV1), total and severe exacerbations and pneumonias. The unit costs of medication, maintenance treatment, exacerbations and pneumonias were obtained for each country. The country-specific analyses adhered to the Finnish, Swedish and Dutch pharmacoeconomic guidelines, respectively.ResultsTreatment with tiotropium/olodaterol gained QALYs ranging from 0.09 (Finland and Sweden) to 0.11 (the Netherlands) versus tiotropium and 0.23 (Finland and Sweden) to 0.28 (the Netherlands) versus LABA/ICS. The Finnish payer’s incremental cost-effectiveness ratio (ICER) of tiotropium/olodaterol was €11 000/QALY versus tiotropium and dominant versus LABA/ICS. The Swedish ICERs were €6200/QALY and dominant, respectively (societal perspective). The Dutch ICERs were €14 400 and €9200, respectively (societal perspective). The probability that tiotropium/olodaterol was cost-effective compared with tiotropium at the country-specific (unofficial) threshold values for the maximum willingness to pay for a QALY was 84% for Finland, 98% for Sweden and 99% for the Netherlands. Compared with LABA/ICS, this probability was 100% for all three countries.ConclusionsBased on the simulations, tiotropium/olodaterol is a cost-effective treatment option versus tiotropium or LABA/ICS in all three countries. In both Finland and Sweden, tiotropium/olodaterol is more effective and cost saving (ie, dominant) in comparison with LABA/ICS.

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Adverse childhood experiences, daytime salivary cortisol, and depressive symptoms in early adulthood: a longitudinal genetically informed twin study

Translational Psychiatry ◽

10.1038/s41398-021-01538-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Eleonora Iob ◽

Jessie R. Baldwin ◽

Robert Plomin ◽

Andrew Steptoe

Keyword(s):

Depressive Symptoms ◽

Hpa Axis ◽

Salivary Cortisol ◽

Adverse Childhood Experiences ◽

Emotional Abuse ◽

Early Adulthood ◽

Cumulative Exposure ◽

Childhood Experiences ◽

Adverse Childhood ◽

Cortisol Levels

AbstractDysregulated hypothalamic–pituitary–adrenal (HPA)-axis function might underlie the relationship between adverse childhood experiences (ACEs) and depression. However, limited research has examined the possible mediating role of the HPA-axis among young people using longitudinal data. Moreover, it remains unclear whether genetic influences could contribute to these associations. Participants were 290 children from the Twins Early Development Study. ACEs were assessed from age 3–11 years. We calculated a cumulative risk score and also derived different ACEs clusters using factor analysis and latent class analysis. HPA-axis activity was indexed by daytime salivary cortisol at age 11. Depressive symptoms were ascertained at age 21. Genetic liability to altered cortisol levels and elevated depressive symptoms was measured using a twin-based method. We performed causal mediation analysis with mixed-effects regression models. The results showed that ACEs cumulative exposure (b = −0.20, p = 0.03), bullying (b = −0.61, p = 0.01), and emotional abuse (b = −0.84, p = 0.02) were associated with lower cortisol levels at age 11. Among participants exposed to multiple ACEs, lower cortisol was related to higher depressive symptoms at age 21 (b = −0.56, p = 0.05). Lower cortisol levels mediated around 10–20% of the total associations of ACEs cumulative exposure, bullying, and dysfunctional parenting/emotional abuse with higher depressive symptoms. Genetic factors contributed to these associations, but the mediation effects of cortisol in the associations of ACEs cumulative exposure (b = 0.16 [0.02–0.34]) and bullying (b = 0.18 [0.01–0.43]) remained when genetic confounding was accounted for. In conclusion, ACEs were linked to elevated depressive symptoms in early adulthood partly through lower cortisol levels in early adolescence, and these relationships were independent of genetic confounding.

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Public health risk analysis of European bat lyssavirus infection in The Netherlands

Epidemiology and Infection ◽

10.1017/s0950268807000167 ◽

2008 ◽

Vol 137 (6) ◽

pp. 803-809 ◽

Cited By ~ 6

Author(s):

K. TAKUMI ◽

P. H. C. LINA ◽

W. H. M. VAN DER POEL ◽

J. A. KRAMPS ◽

J. W. B. VAN DER GIESSEN

Keyword(s):

Public Health ◽

Risk Analysis ◽

The Netherlands ◽

Health Risk ◽

Companion Animals ◽

Public Health Risk ◽

Northern Half ◽

Viral Particles ◽

Bat Rabies ◽

Eptesicus Serotinus

SUMMARYWe present the frequency and the nature of contact incidents of the Serotine bat,Eptesicus serotinus, with humans and with companion animals (specifically cats and dogs), in The Netherlands between 2000 and 2005. Out of 17 bats in bite contact with humans, five tested positive for European bat lyssavirus (EBLV) type 1a. Cats had the most numerous contacts with bats (49 times) but a relatively low number of these bats were EBLV positive (six times). We estimated that the average incidence of human bat rabies infection might be between once per year and once per 700 years, depending mainly on the number of infectious viral particles in bat saliva. The risk of bat rabies is higher between April and October, and in the northern half of the country. This is the first study in Europe describing the risk of human bat rabies after bat contact incidents.

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